Vitamin K2 in electron transport system: are enzymes involved in vitamin K2 biosynthesis promising drug targets?

Abstract

Aerobic and anaerobic respiratory systems allow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents.

Figure 1

Names for quinones and structures of naturally occurring benzoquinones (ubiquinone and plastoquinone) and naphthoquinones (vitamin K₁ and K₂) and representative synthetic vitamin Ks (vitamin K₃, K₄, and K₅).

Figure 2

Vitamin K as a cofactor in blood coagulation systems.

Figure 3

The electron flow system from M. tuberculosis as example of menaquinone mediated energetic pathway.

Figure 4

Biosynthesis of menaquinone.

Figure 5

Schematic representation of mitochondrial electron transport chain and the proposed binding site of atovaquone.

Figure 6

Electron flow in M. tuberculosis and type II NADH dehydrogenase inhibitors.

Figure 7

Representative known respiration inhibitors.

Figure 8

Representative menaquinone biosynthesis inhibitors.